[Prevalence of cataract in 35-64 years old Kaunas city population].
The aim of the study was to determine the prevalence of lens opacity among 35-64 years old Kaunas population as well as to evaluate the stage and type of age-related cataract and its distribution in the groups of age and gender. The material of our study was Kaunas city population aged 35 to 64 years who participated in the scientific Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA-4) study during 2001-2002 in the Laboratory of Population Researches, Institute of Cardiology of Kaunas University of Medicine. During this study random sampling method was used for grouping of 1354 persons according to the age and gender (596 males and 759 females). A total of 2708 lens were examined using the Lens Opacity Classification System (LOCS III) after dilatation of pupils. All the investigated persons were divided into decade age groups: 35-44, 45-54 and 55-64 years. All of them were divided into two groups: with cataract and without. Those who had cataract were divided into three groups according to the three stages of disease. All lenses were divided into seven groups: clear lens, posterior subcapsular, nuclear, cortical and mixed cataract, aphakia and pseudophakia. The lens opacities were present in 106 (17.8%) males and 141 (18.6%) females. The lens opacities of both eyes were observed in 91.3% of investigated persons. In all groups with cataract, the 1st stage comprised 71.6%, 2nd--22.5% and 3rd--6.0% of cases. The prevalence of cataract in decade aged groups according to the stages, respectively in men and women was: among 35-44 years old--1st stage cataract 4.0% and 3.5%, 2nd--unidentified in both groups, 3rd stage--1.0% and unidentified; 45-54 years old--1st stage 9.7% and 9.7%, 2nd--1.0% and 1.1%, 3rd--1.5% and 0.4%; among aged of 55-64 years--the 1st stage as 23.8% and 26.0%, 2nd--9.9% and 11.8%, 3rd--2.0% and 1.5%. In both groups the nuclear cataract dominated (68.2%); in male group--72.4% and female--65.0%. Mixed type comprised 18.3% of cases, respectively 17.9% in males and 18.6% in females, cortical--10.7%, respectively--7.7% and 12.9%; posterior subcapsular--2.8%, respectively--2.8% and 3.4%. The lens opacities were found in 17.8% of males and 18.6% of females among investigated 35-64 years old population of Kaunas city. In the groups of both genders domination of nuclear cataract and the 1st stage of all forms of cataract was observed. The incidence of cataract increases significantly with age.


Predicting responses from Rasch measures.
There is a growing family of Rasch models for polytomous observations. Selecting a suitable model for an existing dataset, estimating its parameters and evaluating its fit is now routine. Problems arise when the model parameters are to be estimated from the current data, but used to predict future data. In particular, ambiguities in the nature of the current data, or overfit of the model to the current dataset, may mean that better fit to the current data may lead to worse fit to future data. The predictive power of several Rasch and Rasch-related models are discussed in the context of the Netflix Prize. Rasch-related models are proposed based on Singular Value Decomposition (SVD) and Boltzmann Machines.


What is targeted proteomics? A concise revision of targeted acquisition and targeted data analysis in mass spectrometry.
Targeted proteomics has gained significant popularity in mass spectrometry-based protein quantification as a method to detect proteins of interest with high sensitivity, quantitative accuracy and reproducibility. However, with the emergence of a wide variety of targeted proteomics methods, some of them with high-throughput capabilities, it is easy to overlook the essence of each method and to determine what makes each of them a targeted proteomics method. In this viewpoint, we revisit the main targeted proteomics methods and classify them in four categories differentiating those methods that perform targeted data acquisition from targeted data analysis, and those methods that are based on peptide ion data (MS1 targeted methods) from those that rely on the peptide fragments (MS2 targeted methods).


Clinical failure after Dresden repair of mid-substance Achilles tendon rupture: human cadaveric testing.
The purpose of this study was to describe the angle of clinical failure during cyclical mobilization exercises in the Achilles tendon of human cadaveric specimens that were repaired using the Dresden technique and FiberWire® No. 2. The secondary aim was to identify the secure limit of mobilization, the type of failure, and the type of apposition. The lower limbs of eight males (mean age: 60.3 ± 6.3 years) were repaired with the Dresden technique following complete, percutaneous mid-substance Achilles tendon rupture. A basal tension of 10 N at 30° of plantarflexion was placed on each specimen. The angle of the ankle during clinical failure (tendon ends separation >5 mm) was then tested via cyclical exercises (i.e. 100 cycles between 30° and 15° of plantarflexion; 100 cycles between 15° of plantarflexion and 0°; 100 cycles between 0° and 15° of dorsiflexion; and 100 cycles between 15° of dorsiflexion and full dorsiflexion). Clinical failure was determined using the Laplacian edge detection filter, and the angle of clinical failure was obtained using a rotatory potentiometer aligned in relation to the intermalleolar axis of each foot specimen. The type of failure (knot, tendon, or suture) and apposition (termino-terminal or non-termino-terminal) were determined. Descriptive statistics were used to obtain the mean; standard deviation; 95 % confidence interval; 1st, 25th, 50th, 75th, and 100th percentiles; and the standard error of the mean for angle data. Proportions were used to describe the type of failure and apposition. The main results were a mean angle of clinical failure equal to 12.5° of plantarflexion, a limit of mobilization equal to 14.0° of plantarflexion, tendon failure type, and non-termino-terminal apposition in all specimens. While the mean angle of clinical failure in human cadaveric models was 12.5° of plantarflexion, after 14.0° of plantarflexion, the percutaneous Dresden technique was found insecure for cyclical mobilization exercises, with a 5 % range of error. These findings are clinically relevant as they provide mechanical limits for diminishing the risk of Achilles lengthening during immediate rehabilitation.


Oxygen saturation monitoring.
Pulse-oximeter is described as the most important technological proceeding for monitoring the patients' safety during anesthesia, after surgery and in emergency. This opinion was widely confirmed in the 1990s when pulse-oximeter has been definitively introduced in the standard for base monitoring in the OR and has been proposed for routinary use also in the ICU. In this paper we consider the importance, in the cardiovascular, respiratory and brain parameters monitoring, of continuous oximetry of mixed venous blood (SVO2) and blood venous saturation in the internal jugular vein (SjvO2).


Regional pulmonary function in supine patients with mitral valve disease.
Supine tidal volume regional ventilation and perfusion images obtained in the posterior and lateral projections demonstrated several alterations in patients with mitral valve disease. Reversal of the gravitational perfusion gradient correlated with pulmonary venous and arterial hypertension; the supine studies reliably distinguished normal subjects from mitral patients. The reversed gradient was from posterior-base to anterior-apex. Focal defects were common and contributed to the reversed gradient in 50% of patients. Perfusion defects larger than those of ventilation, simulating emboli, occurred in 32%, particularly in the middle lobe and superior segment areas. Relative hypoventilation of the left lung was seen in 44% of these patients.


Protective effect of basic fibroblast growth factor on laser induced retinopathy.
To investigate the side effects of the commonly used laser treatment along with testing the neuroprotective effect of bFGF on a potential retinal impairment. To do this, 30 chinchilla pigmented adult male rabbits were divided into the control and experimental groups. The control and experimental groups underwent both laser application and bFGF treatment. The retinal tissue impairment and its renewal rate were tested under the light and electron microscopical levels. The focal laser application on rabbit eyes caused morphological alterations both in the application region and in the neighbouring areas. In the damaged areas, the outer nuclear layer of the neural retina was almost disappeared, retina pigment epithelium was interrupted, the retina pigment epithelium migrated intraretinally, and the damaged region along with neighbouring areas seemed to be not separated. bFGF application just after the laser photocoagulation, revealed better results in application areas. It could be suggested that the bFGF application following laser photocoagulation might have protective, repairing and wound healing effects on the retina.


Morphological effects on the hard palatine mucosa of Calomys callosus submitted to experimental chronic alcoholism.
The morphological effects of ethanol ingestion on the hard palatine mucosa of adult male Calomys callosus were observed. Twenty rodents were divided into two experimental groups: the control group received solid diet, Purina rat chow, and tap water ad libitum; the alcoholic group received the same solid diet and ethanol P.A. diluted 20% in water (v/v). After 270 days of treatment, all animals were sacrificed and the hard palatine mucosa were prepared for TEM and SEM methods. The epithelial cells of the alcoholic group showed some alterations like cytoplasmatic lipid droplets, pycnotic nucleus and increased mitochondrial size. The lamina propria also presented intense lipid droplets accumulation. The morphological changes suggested that chronic ethanol consumption was able to modify the integrity of the mucosa.


Cross sectional echocardiography in determining persistent patency of the ductus arteriosus in preterm infants.
Thirty preterm infants (gestational age 26 to 30 weeks) were investigated by cross sectional echocardiography using a 5 or 7.5 MHz transducer positioned in the suprasternal notch or the left subclavicular position to enable visualisation of the aortic arch, main pulmonary artery, left pulmonary artery, and ductus arteriosus. Each infant was investigated on at least one occasion during both the first and second weeks of life and when possible between the ages of 26 and 31 days. There was prolonged patency of the ductus arteriosus during the first two weeks of life in all infants, and complete closure of the ductus arteriosus occurred only in four patients, all of whom had reached a postconceptional age of 32 to 34 weeks. Eighteen infants received intravenous indomethacin between the age of 5 and 10 days. In these patients ductal narrowing did not occur until a maximum postconceptional age of 29 weeks.


Psychological Burden Among Patients With Inherited Bleeding Disorders in Madinah Province, Saudi Arabia.
Introduction Hereditary bleeding disorders, such as hemophilia and von Willebrand disease (VWD), result from specific deficiencies or malformations in the coagulation cascade proteins. These disorders can significantly impact both physical and psychological health. Complications such as depression, anxiety, and stress (DAS) can further exacerbate these impacts. Despite their significance, detailed prevalence data remain limited, especially for regions such as Madinah province in Saudi Arabia. This study aimed to determine the prevalence of DAS and their associated risk factors among patients with hereditary bleeding disorders in Madinah province, Saudi Arabia. Methods We conducted a cross-sectional study using telephonic interviews involving patients diagnosed with severe hemophilia A or B or VWD attending a hematology clinic in Madinah. Patients over 10 were included, and the study excluded those with central nervous system insults and platelet count concerns. The validated and reliable Depression Anxiety Stress Scale-21-item questionnaire and Statistical Product and Service Solutions (SPSS), version 26.0 (IBM SPSS Statistics for Windows, Armonk, NY), facilitated data collection and analysis, respectively. Results Of the 44 patients studied, 25% exhibited symptoms of depression, 45.5% showed signs of anxiety, and 29.5% had stress symptoms. Regarding symptom severity, 9.1% of patients experienced extremely severe depression, 15.9% had moderate anxiety, and 13.6% reported moderate stress. The prevalence of these psychological issues varied with patients' age and economic status. Notably, a significantly higher rate of depression was observed in patients over 15 years (42.9% vs. 8.7%; p=0.009). Additionally, while not statistically significant, patients with a high economic status reported increased rates of DAS. Conclusions Patients with inherited bleeding disorders, particularly those older than 15, manifest significant psychological distress. There is a pressing need for enhanced awareness, specialized screenings, and tailored counseling services to improve treatment adherence and overall quality of life. Given the findings, a comprehensive national study in Saudi Arabia is highly recommended, alongside the integration of specialized psychological services.


Corticosteroid suppresses urea-cycle-related gene expressions in ornithine transcarbamylase deficiency.
Ornithine transcarbamylase deficiency (OTCD) is most common among urea cycle disorders (UCDs), defined by defects in enzymes associated with ureagenesis. Corticosteroid administration to UCD patients, including OTCD patients, is suggested to be avoided, as it may induce life-threatening hyperammonemia. The mechanism has been considered nitrogen overload due to the catabolic effect of corticosteroids; however, the pathophysiological process is unclear. To elucidate the mechanism of hyperammonemia induced by corticosteroid administration in OTCD patients, we analyzed a mouse model by administering corticosteroids to OTCspf-ash mice deficient in the OTC gene. Dexamethasone (DEX; 20 mg/kg) was administered to the OTCspf-ash and wild-type (WT) mice at 0 and 24 h, and the serum ammonia concentrations, the levels of the hepatic metabolites, and the gene expressions related with ammonia metabolism in the livers and muscles were analyzed. The ammonia levels in Otcspf-ash mice that were administered DEX tended to increase at 24 h and increased significantly at 48 h. The metabolomic analysis showed that the levels of citrulline, arginine, and ornithine did not differ significantly between Otcspf-ash mice that were administered DEX and normal saline; however, the level of aspartate was increased drastically in Otcspf-ash mice owing to DEX administration (P < 0.01). Among the enzymes associated with the urea cycle, mRNA expressions of carbamoyl-phosphate synthase 1, ornithine transcarbamylase, arginosuccinate synthase 1, and arginosuccinate lyase in the livers were significantly downregulated by DEX administration in both the Otcspf-ash and WT mice (P < 0.01). Among the enzymes associated with catabolism, mRNA expression of Muscle RING-finger protein-1 in the muscles was significantly upregulated in the muscles of WT mice by DEX administration (P < 0.05). We elucidated that corticosteroid administration induced hyperammonemia in Otcspf-ash mice by not only muscle catabolism but also suppressing urea-cycle-related gene expressions. Since the urea cycle intermediate amino acids, such as arginine, might not be effective because of the suppressed expression of urea-cycle-related genes by corticosteroid administration, we should consider an early intervention by renal replacement therapy in cases of UCD patients induced by corticosteroids to avoid brain injuries or fatal outcomes.


Damage to Streptococcus lactis resulting from growth at low pH.
Harvey, R. J. (The Dairy Research Institute, Palmerston North, New Zealand). Damage to Streptococcus lactis resulting from growth at low pH. J. Bacteriol. 90:1330-1336. 1965.-Growth of Streptococcus lactis below pH 5.0 results in damage to the cells. A period of growth below pH 5.0 is required before this damage is expressed, and a period of growth above pH 5.0 is required to correct the damage. Part of the damage consists of a reduction in the specific activities of a number of enzymes. At the same time, the differential rate of total protein synthesis is unchanged. During recovery from growth at low pH, the enzymes subject to damage are formed at a differential rate which is higher than normal until the normal specific activities are restored. The growth rate characteristic of the new pH is then resumed. The results are consistent with either of two mechanisms of damage. Growth at low pH could result either in direct inactivation of a number of enzymes, or in loss of control of the differential rates of synthesis of individual enzymes.


Influence of dilution rate and induction of cloned gene expression in continuous fermentations of recombinant yeast.
The effects of growth rate on cloned gene product synthesis in recombinant Saccharomyces cerevisiae have been studied in continuous culture. The plasmid employed contains a yeast GAL10-CYC1 hybrid promoter directing expression of the E. coli lacZ gene. beta-Galactosidase production was therefore controlled by the yeast galactose regulatory circuit, and the induction process and its effects were studied at the various dilution rates. At all dilution rates plasmid stability decreased with induction of lacZ gene expression. In some instances, two induced "steady states" were observed, the first 10-15 residence times after induction and the second after 40-50 residence times. The second induced steady state was characterized by greater biomass concentration and lower beta-galactosidase specific activity relative to the first induced "steady-state." beta-Galactosidase specific activity and biomass concentration increased as dilution rate was reduced, and despite lower flow rate and plasmid stability, overall productivity (activity/L/hr) was substantially higher at low dilution rate. Important factors influencing all of the trends were the glucose and galactose (inducer) concentrations in the vessel and inducer metabolism.


Cordycepin negatively modulates lipopolysaccharide-induced cytokine production by up-regulation of heme oxygenase-1.
The present study is to investigate the effect of cordycepin on the expression of heme oxygenase-1 (HO-1) in lipopolysaccharide (LPS)-activated microphages, as well as its mechanism of action. Mouse RAW264.7 cells were treated with different concentrations of cordycepin for 0-16h. Western blotting was used to determine the expression of HO-1 and the phosphorylation of c-Src and the p47phox subunit of NADPH oxidase. Intracellular reactive oxygen species (ROS) level was determined using H2DCFDA as fluorescent probe. Laser-scanning confocal microscopy was used to visualize the nuclear translocation of NF-E2-related factor 2 (Nrf2). Enzyme-linked immunosorbent assay was performed to measure the inhibitory effect of cordycepin on LPS-induced secretion of tumor necrosis factor-α and interleukin-6. Cordycepin induced the phosphorylation of c-Src and p47phox subunit of NADPH oxidase in RAW264.7 cells. Cordycepin increased the secretion of ROS by activating NADPH oxidase. In addition, cordycepin enhanced the expression of HO-1 in RAW264.7 cells in both dose- and time-dependent manners. Of note, elevated HO-1 expression induced by cordycepin treatment was regulated by c-Src/NADPH oxidase/ROS pathway. HO-1 expression induced by cordycepin was dependent on the activation of Nrf2, which was regulated by c-Src/NADPH oxidase/ROS. Cordycepin reduced LPS-induced secretion of proinflammatory cytokines through up-regulation of HO-1. The present study demonstrates that cordycepin induces the expression of HO-1 in RAW264.7 cells via c-Src/NADPH oxidase/ROS/Nrf2 pathway, and plays an anti-inflammatory role by inhibiting the secretion of cytokines from macrophages.


Risk of bias in studies investigating novel diagnostic biomarkers for heart failure with preserved ejection fraction. A systematic review.
Diagnosing heart failure with preserved ejection fraction (HFpEF) in the non-acute setting remains challenging. Natriuretic peptides have limited value for this purpose, and a multitude of studies investigating novel diagnostic circulating biomarkers have not resulted in their implementation. This review aims to provide an overview of studies investigating novel circulating biomarkers for the diagnosis of HFpEF and determine their risk of bias (ROB). A systematic literature search for studies investigating novel diagnostic HFpEF circulating biomarkers in humans was performed up until 21 April 2020. Those without diagnostic performance measures reported, or performed in an acute heart failure population were excluded, leading to a total of 28 studies. For each study, four reviewers determined the ROB within the QUADAS-2 domains: patient selection, index test, reference standard, and flow and timing. At least one domain with a high ROB was present in all studies. Use of case-control/two-gated designs, exclusion of difficult-to-diagnose patients, absence of a pre-specified cut-off value for the index test without the performance of external validation, the use of inappropriate reference standards and unclear timing of the index test and/or reference standard were the main bias determinants. Due to the high ROB and different patient populations, no meta-analysis was performed. The majority of current diagnostic HFpEF biomarker studies have a high ROB, reducing the reproducibility and the potential for clinical care. Methodological well-designed studies with a uniform reference diagnosis are urgently needed to determine the incremental value of circulating biomarkers for the diagnosis of HFpEF.


Faculty practice: a model to bridge the theory-practice divide.
It has been suggested that as a result of nurse education withdrawing from the clinical setting and becoming established in institutions of higher education, there has been a separation of theory from practice. Recognition of the theory-practice gap by clinicians and professional bodies has led to calls for nurse educators to retain a clinical focus. Faculty practice is described and critically discussed as a model of practice to bridge the theory-practice divide. In this article, the author presents the results of a 6-month pilot study to implement such a model within a community trust, and suggests that the development of such initiatives will foster collaborative working and improve nurse education and patient care.


Multidimensional dosimetry of ¹⁰⁶Ru eye plaques using EBT3 films and its impact on treatment planning.
The purpose of this study was to establish a method to perform multidimensional radiochromic film measurements of (106)Ru plaques and to benchmark the resulting dose distributions against Monte Carlo simulations (MC), microdiamond, and diode measurements. Absolute dose rates and relative dose distributions in multiple planes were determined for three different plaque models (CCB, CCA, and COB), and three different plaques per model, using EBT3 films in an in-house developed polystyrene phantom and the mcnp6 MC code. Dose difference maps were generated to analyze interplaque variations for a specific type, and for comparing measurements against MC simulations. Furthermore, dose distributions were validated against values specified by the manufacturer (BEBIG) and microdiamond and diode measurements in a water scanning phantom. Radial profiles were assessed and used to estimate dosimetric margins for a given combination of representative tumor geometry and plaque size. Absolute dose rates at a reference depth of 2 mm on the central axis of the plaque show an agreement better than 5% (10%) when comparing film measurements (mcnp6) to the manufacturer's data. The reproducibility of depth-dose profile measurements was <7% (2 SD) for all investigated detectors and plaque types. Dose difference maps revealed minor interplaque deviations for a specific plaque type due to inhomogeneities of the active layer. The evaluation of dosimetric margins showed that for a majority of the investigated cases, the tumor was not completely covered by the 100% isodose prescribed to the tumor apex if the difference between geometrical plaque size and tumor base ≤4 mm. EBT3 film dosimetry in an in-house developed phantom was successfully used to characterize the dosimetric properties of different (106)Ru plaque models. The film measurements were validated against MC calculations and other experimental methods and showed a good agreement with data from BEBIG well within published tolerances. The dosimetric information as well as interplaque comparison can be used for comprehensive quality assurance and for considerations in the treatment planning of ophthalmic brachytherapy.


In vitro osteogenesis process induced by hybrid nanohydroxyapatite/graphene nanoribbons composites.
Carbon nanotubes combine high bend and mechanical strength, which is advantageous for many structural and biomedical purposes. Recently, some biomaterials, based on carbon nanostructures and nanohydroxyapatite (nHAp), have been investigated as bone substitutes in order to improve regeneration. The aim of this study was to access the expression of some RNA transcripts (involved in the process of osteoblast differentiation) by mesenchymal stem cells cultured over different nanocomposite surfaces. A multi-walled carbon nanotube (MWCNT) was firstly grown using chemical vapor deposition and then exfoliated using chemical and oxygen plasma treatments to obtain graphene nanoribbons (GNR). The hybrid composites nHAp/GNR were prepared using the wet method assisted by ultrasound irradiation with different amounts of GNR (1.0, 2.0 and 3.0 wt %). Five groups were tested in cell cultures. Group 1: synthesized nHAp; Group 2: synthesized GNR; Group 3: nHAp and 1.0% of GNR; Group 4: nHAp and 2.0% of GNR and group 5: nHAp and 3.0% of GNR. Real time reverse transcription polymerase chain reactions were performed, and all data was submitted to Kruskal Wallis and Dunn tests, at a significance level of 5%. As a result, three nanocomposites with different proportions of GNR were successfully produced. After cell culture, the expression of osteogenic genes demonstrated no significant differences among the groups and periods. However, bone morphogenetic protein II (BMP II), integrin binding sialoprotein (IBSP), and Osterix highest expressions were observed in the group containing 3.0% of GNR. In conclusion, our hybrid composites may be useful in bone interventions requiring mesenchymal stem cell differentiation into osteoblasts for healing.


Developmental Changes in Young Children's Conceptions of Friendship.
The present study examined the development of friendship conceptions from 4 to 7 years of age. Subjects were administered an open-ended interview, a picture recognition task, and a forced-choice rating task in which they identified the most important characteristics of friendship. Common activities, affection, support, and propinquity were all found to be salient aspects of most children's conceptions. Friendship expectations concerning affection and support increased m frequency with age, while references to physical characteristics decreased. In general, parallel findings were found on the 3 measures, although the results were not as strong on the open-ended interview. The findings suggest that children first learn the overt characteristics of the occupants of the role of friend, but as they grow older they place increasing emphasis on affectively based characteristics.


The burden of non-communicable diseases among people living with HIV in Sub-Saharan Africa: a systematic review and meta-analysis.
Non-communicable diseases (NCDs) are increasing among people living with HIV (PLHIV), especially in Sub-Saharan Africa (SSA). We determined the prevalence of NCDs and NCD risk factors among PLHIV in SSA to inform health policy makers. We conducted a systematic review and meta-analysis on the prevalence of NCDs and risk factors among PLHIV in SSA. We comprehensively searched PubMed/MEDLINE, Scopus, and EBSCOhost (CINAHL) electronic databases for sources published from 2010 to July 2023. We applied the random effects meta-analysis model to pool the results using STATA. The systematic review protocol was registered on PROSPERO (registration number: CRD42021258769). We included 188 studies from 21 countries in this meta-analysis. Our findings indicate pooled prevalence estimates for hypertension (20.1% [95% CI:17.5-22.7]), depression (30.4% [25.3-35.4]), diabetes (5.4% [4.4-6.4]), cervical cancer (1.5% [0.1-2.9]), chronic respiratory diseases (7.1% [4.0-10.3]), overweight/obesity (32.2% [29.7-34.7]), hypercholesterolemia (21.3% [16.6-26.0]), metabolic syndrome (23.9% [19.5-28.7]), alcohol consumption (21.3% [17.9-24.6]), and smoking (6.4% [5.2-7.7]). People living with HIV have a high prevalence of NCDs and their risk factors including hypertension, depression, overweight/obesity, hypercholesterolemia, metabolic syndrome and alcohol consumption. We recommend strengthening of health systems to allow for improved integration of NCDs and HIV services in public health facilities in SSA. NCD risk factors such as obesity, hypercholesterolemia, and alcohol consumption can be addressed through health promotion campaigns. There is a need for further research on the burden of NCDs among PLHIV in most of SSA. This study did not receive any funding.


Phenylalanine Interacts with Oleic Acid-Based Vesicle Membrane. Understanding the Molecular Role of Fibril-Vesicle Interaction under the Context of Phenylketonuria.
In the present contribution, on the basis of a spectroscopic and microscopic investigation, the characterization and photophysics of various assemblies of oleic acid/oleate solution at three pH values, namely, 8.28, 9.72, and 11.77, were explored. The variation in the dynamic response of aqua molecules in and around the assemblies has been interrogated by a picoseconds solvation dynamics experiment using a time-correlated single-photon counting setup employing coumarin-153 as a probe. On the one hand, the time-resolved fluorescence anisotropy measurement along with the fluorescence correlation spectroscopy experiment was executed to extract information regarding the comparison of the extent of the internal restricted confinement of these assemblies. On the other hand, an effort to investigate the cross-interaction between the self-assembled architectures of l-phenylalanine (l-Phe), responsible for phenylketonuria (PKU) disorder, and the oleic acid at the vesicle-forming pH established that the l-Phe fibrillar morphologies strongly alter the dynamic properties of the vesicle membrane formed by the oleic acid. Specifically, the interaction of the l-Phe assemblies with the oleic acid vesicle membrane is found to introduce the flexibility of the vesicle membrane and alter the hydration properties of the membrane. To track the fibril-induced alterations of the oleic acid vesicle properties, various spectroscopic and microscopic investigations were performed. The mutual reconciliation of the experimental outputs, therefore, portrays the state of the art, which accounts for the fibril-induced alterations of the properties of the oleic acid vesicle membrane, the mimicking setup of the cellular membrane, thereby informing us that alterations of such a property of the membrane should be taken into active consideration during the rational development of therapeutic modulators against disorders like PKU.


Psychiatric disorder in children with birth anomalies. A retrospective follow-up study.
A group of 273 children and adolescents, aged 8 to 19 years, who had been treated for a congenital malformation during their 1st month of life, were studied using psychiatric interviews with the child and at least one of his parents. The child was also given a Wechsler intelligence test. The rate of psychopathological disturbance was as high as 49% (the classification used included organic brain disorder and mental retardation). Developmental deviations, psychoneurotic disorder and reactive disorder were the commonest types of disturbance (in 18, 17, and 11% respectively). Eleven percent were suffering from organic brain disorder and 8% had an IQ of no more than 50. The malformed children were compared with 509 children from the general population in terms of behaviour disturbance as rated by their teacher. Approximately one child in five in both groups presented behaviour problems, and behaviour was labelled as antisocial in 10% of children in both groups. The two groups of children did not differ significantly in regard to the family's social class, annual income, father's educational background, or the number of children in the family, but the parents of the malformed children had recieved psychiatric treatment more often than the control group parents.


Do tigers hunt during the day? Diel activity of the Asian tiger mosquito, Aedes albopictus (Diptera: Culicidae), in urban and suburban habitats of North America.
Aedes (Stegomyia) albopictus (Skuse) impacts human outdoor activity because of its aggressive biting behavior, and as a major vector of mosquito-borne diseases, it is also of public health importance. Although most mosquito species exhibit crepuscular activity by primarily host seeking at dawn and dusk, Ae. albopictus has been traditionally characterized as a diurnal or day-biting mosquito. With the global expansion and increased involvement of Ae. albopictus in mosquito-borne diseases, it is imperative to elucidate the diel activity of this species, particularly in newly invaded areas. Human sweep netting and carbon dioxide-baited rotator traps were used to evaluate the diel activity of Ae. albopictus in two study sites. Both trapping methods were used in New Jersey's Mercer County, USA (temperate/urban), while only human sweep netting was used in Florida's Volusia County, USA (subtropical/suburban). Human sweep netting was performed to determine adult mosquito activity at Sunrise, Solar Noon, Sunset, and Lunar Midnight. Because New Jersey is in a temperate area, diel activity was investigated during the early season (3-19 July), peak season (25 July-19 September), and late season (22 September- 22 October). Aedes albopictus showed the highest activity during peak and late seasons at Solar Noon (P < 0.05). At Sunrise and Sunset during the peak season, Ae. albopictus activity was similar. Lunar Midnight activity was significantly lower than Sunrise and Solar Noon (P < 0.05) but was similar to that of Sunset. In the late season, the highest activity was observed during Solar Noon while the least activity was observed during Sunrise and Lunar Midnight (P<0.05). Bottle rotator traps used in conjunction with the human sweep net technique exhibited similar results. Seasonal activity was not differentiated in Florida due to the consistent subtropical climate. The highest adult activity was observed at Sunrise using human sweep netting, but it was not significantly different from Solar Noon and Sunset. The lowest adult activity was observed at Lunar Midnight; however, it was not significantly different from Solar Noon and Sunset. These results provide evidence that the diel activity of Ae. albopictus, contrary to the common perception of its diurnal activity, is much more varied. Involvement of Ae. albopictus in the transmission of debilitating mosquito-borne pathogens such as chikungunya, dengue, and Zika virus, coupled with its affinity to thrive in human peridomestic environments, substantiates that our findings have global implications in areas where Ae. albopictus populations established. It also highlights the importance of behavioral studies of vector species which will not only help mosquito control professionals plan the timing of their control efforts but also provides empirical evidence against conventional wisdoms that may unjustly persist within public health stewards.


Immunoprofiling toll-like receptor ligands: Comparison of immunostimulatory and proinflammatory profiles in ex vivo human blood models.
There is a pressing need for the development of novel, safe and effective adjuvants. The recent discovery and characterization of pathogen-associated molecular pattern (PAMP)-recognizing elements such as the Toll-like, NOD-like and RIG-like receptors, has brought into sharp focus the role of PAMPs in bridging the innate and adaptive immune responses, and a detailed understanding of the immunostimulatory vis-à-vis proinflammatory activities could lead to the development of effective adjuvants, monophosphoryl lipid A being an excellent example. We describe in this paper a series of hierarchical assays that were employed to characterize TLR agonists in vitro including primary TLR-reporter assays, secondary indices of immune activation, and tertiary screens characterizing transcriptomal activation patterns to identify optimal immunostimulatory chemotypes. The evaluation of representative members of known human TLR agonists demonstrate that TLR2, -4, -5 and -7 agonists were immunostimulatory. TLR7 agonists were extremely immunostimulatory, stimulating nearly all subsets of lymphocytes without inducing proinflammatory cytokine responses. The TLR5 agonist, flagellin, while immunostimulatory, was also highly proinflammatory. These results suggest that TLR agonists other than lipid A-like chemotypes could be developed into potential adjuvants, and that this series of hierarchical assays could be adapted to rapidly identify in large libraries, compounds with adjuvantic potential that lack proinflammatory responses.


The effects of ice on blood flow and bone metabolism in knees.
The effects of an ice wrap, applied to a knee for 20 minutes, on blood flow and bone metabolism were measured using triple-phase technetium bone scans. Twenty-one subjects between 29 and 63 years of age were studied. A commercially available ice wrap was applied to one knee 20 minutes before scanning, while an identical wrap left at room temperature was applied to the opposite knee to act as a control. Scans of the knees were obtained at the completion of cooling, and the images were quantified by computer image analysis for each knee at each phase of the scan. Percentage of decrease in blood flow and subsequent bone uptake of technetium for the iced knee as compared with the opposite knee were calculated. All iced knees demonstrated decreased arterial and soft tissue blood flow as well as decreased bone uptake, which is a reflection of changes in both bone blood flow and metabolism. The average decrease was 38.4% +/- 4.97 in arterial blood flow, 25.8% +/- 2.04 in soft tissue blood flow, and 19.3% +/- 2.0 (standard error of the mean in each) in bone uptake. This "ice effect" was not related to age, sex, knee circumference, or skin temperature after cooling. By decreasing blood flow and cell metabolism, ice theoretically can limit hemorrhage and cell death in the setting of acute traumatic injury. This study thus provides a scientific rationale for the use of ice as tested for such injuries to a large joint, whether in the soft tissues or bones.


Paediatric meningococcaemia in northwestern Ontario, Canada: a case for publicly funded meningococcal B vaccination.
Neisseria meningitidis serogroup B is an important infectious agent in developed countries, including Canada. Infants are particularly susceptible to infection with serogroup B because of immature immune systems, pathogen virulence factors and changing serogroup dynamics in the post-vaccination era. Currently, the Ontario provincial government does not include serogroup B in its routine publicly funded meningococcal vaccination program. A formerly well 14-month-old male presented to a tertiary hospital emergency department with fever, minor respiratory problems, diffuse purpuric rash, distended abdomen, tachycardia, and history of one episode of vomiting and melena each. Meningococcaemia was immediately suspected, and he was treated with ceftriaxone, cefotaxime and vancomycin before transfer to a different acute care facility within 12 h. N. meningitidis serogroup B, sensitive to ceftriaxone and penicillin, was identified in his blood. The patient developed gangrene of the lower legs and underwent bilateral below-knee amputation 8 days post-admission. This instance of meningococcaemia with extensive sequelae is an example of the various serious outcomes of meningococcal infection. It provides persuasive reason for routine publicly funded vaccination against N. meningitidis serogroup B in Ontario.


The effect of case rate and coinfection rate on the positive predictive value of a registry data-matching algorithm.
Statistical modeling has suggested that the prevalence of false matches in data matching declines as the events become rarer or the number of matches increases. We examined the effect of case rate and coinfection rate in the population on the positive predictive value (PPV) of a matching algorithm for HIV/AIDS and sexually transmitted disease (STD) surveillance registry data. We used LinkPlus™, a probabilistic data-matching program, to match HIV/AIDS cases diagnosed in New York City (NYC) from 1981 to March 31, 2012, and reported to the NYC HIV/AIDS surveillance registry against syphilis and chlamydia cases diagnosed in NYC from January 1 to June 30, 2010, and reported to the NYC STD registry. Match results were manually reviewed to determine true matches. With an agreement/disagreement comparison score cutoff value of 10.0, LinkPlus identified 3,013 matches, of which 1,582 were determined to be true by manual review. PPV varied greatly in subpopulations with different case rates and coinfection rates. PPV was the highest (91.6%) in male syphilis cases, who had a relatively low case rate but a high HIV coinfection rate, and lowest (18.0%) in female chlamydia cases, who had a high case rate but a low HIV coinfection rate. When the cutoff value was increased to 15.0, PPVs in male syphilis and female chlamydia cases increased to 98.3% and 90.5%, respectively. Case rates and coinfection rates have a significant effect on the PPV of a registry data-matching algorithm: PPV decreases as the case rate increases and coinfection rate decreases. Before conducting registry data matching, program staff should assess the case rate and coinfection rate of the population included in the data matching and select an appropriate matching algorithm.


Granulocyte-macrophage colony-stimulating factor augments the primary antibody response by enhancing the function of antigen-presenting cells.
Purified, recombinant-derived murine granulocyte-monocyte colony-stimulating factor was found to enhance the primary in vitro immune response to SRBC by murine spleen cells. In determining the mechanism of this augmentation, it was found that only splenic adherent cells and neither resting nor activated T cells nor B cells expressed specific receptors for GM-CSF. When splenic adherent cells were pulsed briefly with GM-CSF before addition to macrophage-depleted cultures, they reconstituted the PFC response to a significantly greater degree than did control macrophages. Splenic adherent cells incubated overnight with SRBC plus GM-CSF were also more efficient antigen-presenting cells than splenic adherent cells incubated with antigen alone. The mechanism of this enhanced antigen presentation was found to be due to a GM-CSF-dependent increase in the level of IL 1 secretion and Ia antigen expression. Consistent with these data was the finding that GM-CSF augmented IL 2 production by splenic T cells in response to suboptimal concentrations of Con A. Finally, the day 5 in vivo antibody response (as measured by serum titers) of mice immunized with a low dose of SRBC was enhanced by two daily inoculations of GM-CSF. Thus, the role that GM-CSF plays in augmenting immune responses may not be solely accounted for by its ability to cause the proliferation or differentiation of macrophages, but more than likely includes its ability to enhance the function of antigen-presenting macrophages.


Genotypes and antibiotic resistance of bovine Campylobacter and their contribution to human campylobacteriosis.
Campylobacter jejuni and Campylobacter coli are the most important bacterial causes of human gastroenteritis. Chicken has been recognized as a major source for human infection, whereas cattle might also contribute to a lesser extent. However, there is a paucity of information available regarding Campylobacter in Swiss cattle and their role for human campylobacteriosis. To gain more information on genotypes and antibiotic resistance of bovine C. jejuni and C. coli and on their contribution to human disease, 97 cattle isolates were analysed. Multilocus sequence typing (MLST) and flaB typing were applied and the gyrA and 23S rRNA genes were screened for point mutations responsible for quinolone and macrolide resistance, respectively. A total of 37 sequence types (STs) and 44 flaB types were identified, including two sequence types and five flaB types not previously described. Most common sequence types were ST21 (21%), ST61 (12%) and ST48 (11%). Only one isolate was macrolide resistant while 31% (n = 30) were quinolone resistant. Source attribution indicated chicken as the main source of human infection with cattle being second. In conclusion, cattle should not be underestimated as a potential source of human campylobacteriosis.


Papillary fibroelastoma of the interatrial septum: a case report.
Primary cardiac tumors are rare, with benign lesions outnumbering malignant ones by a margin of over four to one. Amongst the benign cardiac neoplasms, papillary fibroelastomas are reported second only to myxomas. Papillary fibroelastomas commonly rise from heart valves and their size ranges from a few millimeters to well over 2.0 cm in diameter. While myxomas commonly arise from the interatrial septum, we present the rare example of a large papillary fibroelastoma arising from the left side of the interatrial septum.


[Cystic adenoid carcinoma. Apropos of 2 cases originating in the salivary glands].
The CAQ is a tumor of the major and minor salivary glands, of superior airway glands, uterine cervix glands, and the Bartholin glands of the vulva. However, recently, primary cases of CAQ of the skin, originating in eccrine sweat glands were described. We report 2 CAQ cases, one, case 1, of minor salivary glands of the palate, that by extension, reached the skin of the face, finishing with kidney metastasis; and its histological type corresponded to the cribiform variety in both the primary tumor and the kidney metastasis. Case 2 presented in the parotid gland and its histological type is the solid variety of the CAQ.


Three-dielectric-layer hybrid solvation model with spheroidal cavities in biomolecular simulations.
This paper extends the three-dielectric-layer hybrid solvation model for treating electrostatic interactions in biomolecular simulations from the spherical geometry [Comm. Comp. Phys. 6, 955 (2009)] to the prolate/oblate spheroidal geometries. In the resulting model, the inner spheroidal cavity of a low dielectric constant epsilon(i) contains an irregular-shaped solute and some explicit solvent molecules, while the unbounded outer layer is used to implicitly model the bulk solvent as a dissimilar continuum medium of a high dielectric constant epsilon(o). The thin intermediate translation layer, which also consists of explicit solvent molecules, assumes a continuous variation of the dielectric permittivity epsilon(r) changing smoothly from epsilon(i) to epsilon(o). In particular, the so-called quasiharmonic dielectric permittivity profile is introduced based on a harmonic interpolation, thus allowing analytical series solutions of the generalized Coulomb potential and the self-polarization energy in terms of the associated Legendre functions. A key advantage of the proposed quasiharmonic dielectric model lies in the fact that it overcomes the inherent mathematical divergence in the self-polarization energy that exists in the simple and widely used steplike dielectric model. Numerical examples are included to show some simulated behaviors of the quasiharmonic dielectric model and the corresponding analytical solution.


Incidence of Stroke in Immigrants to Canada: A Province-wide Retrospective Analysis.
To evaluate the association between immigration status and stroke incidence. We conducted a retrospective cohort study of 8 million adults (15% immigrants) residing in Ontario, Canada on January 1, 2003, with no history of prior stroke or transient ischemic attack (TIA). Subjects were followed until March 31, 2018 to identify incident stroke or TIA, defined as hospitalization or emergency room visit. We calculated adjusted hazard ratios (HR) of stroke or TIA in immigrants compared to long-term residents using cause-specific hazard models, adjusting for demographics and comorbidities. We evaluated whether the association varied by age, stroke type or country of origin of immigrants. During 109 million person-years follow-up, we observed 235,336 incident stroke or TIA events. Compared to long-term residents, immigrants had a lower rate of stroke or TIA (10.9 vs. 23.4 per 10,000 person-years, HR 0.67; 0.66-0.68). This was true across all age groups and stroke types, with a HR in immigrants vs. long-term residents for ischemic stroke of 0.71 (0.69-0.72), intracerebral hemorrhage 0.89 (0.85-0.93), subarachnoid hemorrhage 0.85 (0.81-0.91), and TIA 0.53 (0.51-0.54). The magnitude of the reduction in stroke risk associated with immigration status was less pronounced in immigrants from the Caribbean (HR 0.95; 0.91-1.00), Latin America (HR 0.85;0.82-0.91) and Africa (HR 0.80; 0.74-0.85) than in those from other world regions. Immigrants have a lower rate of stroke or TIA than long-term residents with variation by age, stroke type and country of origin. This knowledge may be useful for developing targeted primary stroke prevention strategies.


Daily nonaccidental mortality associated with short-term PM2.5 exposures in Delhi, India.
Ambient particulate matter of aerodynamic diameter less than 2.5 microns PM2.5) levels in Delhi routinely exceed World Health Organization (WHO) guidelines and Indian National Ambient Air Quality Standards (NAAQS) for acceptable levels of daily exposure. Only a handful of studies have examined the short-term mortality effects of PM in India, with none from Delhi examining the contribution of PM2.5. We aimed to analyze the association between short-term PM2.5 exposures and daily nonaccidental mortality in Delhi, India. Using generalized additive Poisson regression models, we examined the association between daily PM2.5 exposures and nonaccidental mortality between June 2010 and December 2016. Daily exposures to PM2.5 were estimated using an ensemble averaging technique developed by our research group, and mortality data were obtained from the Municipal Corporations of Delhi and the New Delhi Municipal Council. Median exposures to PM2.5 were 91.1 µg/m3 (interquartile range = 68.9, 126.2), with minimum and maximum exposures of 21.4 µg/m3 and 276.7 µg/m3, respectively. Total nonaccidental deaths recorded in Delhi during the study period were 700,512. Each 25 µg/m3 increment in exposure was associated with a 0.8% (95% confidence intervals [CI] = 0.3, 1.3%) increase in daily nonaccidental mortality in the study population and a 1.5% (95% CI = 0.8, 2.2%) increase in mortality among those with 60 years of age or over. The exposure-response relationship was nonlinear in nature, with relative risk rising rapidly before tapering off above 125 µg/m3. Meeting WHO guidelines for acceptable levels of exposure over the study period would have likely averted 17,526 (95% CI = 6,837, 25,589) premature deaths, with older and male populations disproportionately affected. This study provides robust evidence of the impact of short-term exposure to PM2.5 on nonaccidental mortality with important considerations for various stakeholders including policymakers and physicians. Most importantly, we find that reducing exposures significantly below current levels would substantially decrease the mortality burden associated with PM2.5.


Legionnaires' disease and gardening.
Legionella longbeachae was cultured from the sputum of a patient suffering from Legionnaires' disease. Source identification efforts included analysis of samples of potting soil from the patient's garden, and a genotypically indistinguishable strain of L. longbeachae was cultured from this material. Following examination of a national collection of Legionella isolates, two more patients with indistinguishable genotypes were identified. One of these patients had visited a garden centre in the same municipality in which the index patient had acquired his potting soil. The study demonstrated the value of systematic collection of identification data and patient isolates over a prolonged period.


[Multidisciplinary management of postpartum headaches].
Headache is a common complaint in the postpartum period and is benign in most cases. Physiological adaptations during pregnancy and childbirth put women at risk of secondary headaches and the clinician must be able to identify them at an early stage. The management algorithm described in this article provides a systematic assessment based on 4 key points: the clinical presentation, which refers to specific clinical pictures or severity criteria, the clinical context and the evolution of symptoms focusing on potential complications and known associations between different diseases. Indications for imaging (CT or MRI) and possible treatments during breastfeeding are also detailed.


The carboxy-terminus of protein 4.1r resembles Beta-tubulin.
The protein 4.1R is an isoform of a larger family of 4.1 proteins. It is known as a component of the plasma membrane skeleton, but it is also found at the centrosomes in interphase and mitosis. To investigate the properties of the carboxy terminal region of protein 4.1R, we raised antibodies against a peptide representing the last 14 amino acids of 4.1R. These antibodies crossreact with an epitope in beta-tubulin and stain the microtubule network by immunofluorescence. Furthermore, sequence comparison of the carboxy terminal 4.1R peptide sequence with tubulin reveals homology with a region at the end of helix 5 in beta-tubulin, but not alpha-tubulin. A potential function of the 4.1R carboxy terminus in regulating the formation of microtubule networks is discussed.


Emotionally clocked out: cell-type specific regulation of mood and anxiety by the circadian clock system in the brain.
Circadian rhythms are self-sustained oscillations of biological systems that allow an organism to anticipate periodic changes in the environment and optimally align feeding, sleep, wakefulness, and the physiological and biochemical processes that support them within the 24 h cycle. These rhythms are generated at a cellular level by a set of genes, known as clock genes, which code for proteins that inhibit their own transcription in a negative feedback loop and can be perturbed by stress, a risk factor for the development of mood and anxiety disorders. A role for circadian clocks in mood and anxiety has been suggested for decades on the basis of clinical observations, and the dysregulation of circadian rhythms is a prominent clinical feature of stress-related disorders. Despite our understanding of central clock structure and function, the effect of circadian dysregulation in different neuronal subtypes in the suprachiasmatic nucleus (SCN), the master pacemaker region, as well as other brain systems regulating mood, including mesolimbic and limbic circuits, is just beginning to be elucidated. In the brain, circadian clocks regulate neuronal physiological functions, including neuronal activity, synaptic plasticity, protein expression, and neurotransmitter release which in turn affect mood-related behaviors via cell-type specific mechanisms. Both animal and human studies have revealed an association between circadian misalignment and mood disorders and suggest that internal temporal desynchrony might be part of the etiology of psychiatric disorders. To date, little work has been conducted associating mood-related phenotypes to cell-specific effects of the circadian clock disruptions. In this review, we discuss existing literature on how clock-driven changes in specific neuronal cell types might disrupt phase relationships among cellular communication, leading to neuronal circuit dysfunction and changes in mood-related behavior. In addition, we examine cell-type specific circuitry underlying mood dysfunction and discuss how this circuitry could affect circadian clock. We provide a focus for future research in this area and a perspective on chronotherapies for mood and anxiety disorders.


Small-molecule inhibitors of bone morphogenic protein and activin/nodal signals promote highly efficient neural induction from human pluripotent stem cells.
The balance of bone morphogenic protein (BMP), transforming growth factor-β (TGFβ)/activin/nodal, and Wnt signals regulates the early lineage segregation of human embryonic stem cells (ESCs). Here we demonstrate that a combination of small-molecule inhibitors of BMP (Dorsomorphin) and TGFβ/activin/nodal (SB431542) signals promotes highly efficient neural induction from both human ESCs and induced pluripotent stem cells (iPSCs). The combination of small molecules had effects on both cell survival and purity of neural differentiation, under conditions of stromal (PA6) cell coculture and feeder-free floating aggregation culture, for all seven pluripotent stem cell lines that we studied, including three ESC and four iPSC lines. Small molecule compounds are stable and cost effective, so our findings provide a promising strategy for controlled production of neurons in regenerative medicine.


What can reunification of East and West Germany tell us about the cause of the allergy epidemic?
The increase of allergies in East Germany--reaching West German prevalence shortly after the reunification--is considered a model for the allergy epidemic in the western world. Whether such a pattern was observed in all comparison studies and for all allergic manifestations is not known because a complete overview is missing. Hints about possible causal factors for the allergy epidemic could be gained by identifying known risk factors, which explain the observed pattern of allergy development in Germany. Again, an overview about these efforts is missing. We identified 14 cross-sectional studies conducted after 1989 and calculated prevalence ratios (West/East) for asthma, hayfever, eczema and allergic sensitization. Additionally, a tabular overview about the explanatory power of risk factors hypothesized in the nineties and covering outdoor exposure, indoor factors, early childhood influences, nutrition as well as awareness is given. At the time of the German reunification, the prevalence ratio West/East was largest for hayfever and sensitization to birch pollen, less pronounced for the other phenotypes and even less than one for atopic eczema. Hayfever and sensitization to birch pollen also showed the steepest increase in East Germany afterwards. Single-room heating with fossil fuels and living as only child in a family were identified as explaining up to 23.5% of the excess trend in East compared to the trend in West. Hayfever as most typical atopic disease showed the difference in allergy pattern between East and West Germany clearest. Risk factors identified for these phenotypes are completely different (single child) or even act in the opposite direction (single-room heating) from classical risk factors for airway diseases. This might be the most important lesson from the West/East German experience. It already stimulated many other studies focussing on protective factors such as microbial stimulation.


Wall-anchored semiflexible polymer under large amplitude oscillatory shear flow.
The properties of semiflexible polymers tethered by one end to an impenetrable wall and exposed to oscillatory shear flow are investigated by mesoscale simulations. A polymer, confined in two dimensions, is described by a linear bead-spring chain, and fluid interactions are incorporated by the Brownian multiparticle collision dynamics approach. At small strain, the polymers follow the applied flow field. However, at high strain, we find a strongly nonlinear response with major conformational changes. Polymers are stretched along the flow direction and exhibit U-shaped conformations while following the flow. As a consequence of confinement in the half-space, frequency doubling in the time-dependent polymer properties appears along the direction normal to the wall.


Painless angioleiomyoma: a case report with review of literature.
A 55 year old male, who presented with a painless swelling of six months duration on his thigh, was clinically diagnosed to have a benign soft tissue neoplasm. Histological examination of the excision biopsy specimen revealed a benign tumour of the vascular smooth muscle, which was diagnosed as angioleiomyoma. Angioleiomyomas are painful lesions that can occur anywhere in the body. We present this case for its atypical clinical presentation and discuss its histologic features with a review of literature.


Manganese chloride-induced G0/G1 and S phase arrest in A549 cells.
In the present study, we investigated the effects of manganese chloride (MnCl2) on cell cycle progression in A549 cells used as a model of Mn-induced lung toxicity. Cells were treated with various concentrations of MnCl2 (0, 0.01, 0.1, 0.5, 1.0 or 2.0 mM) for 24, 48 or 72 h. Cell proliferation was determined with MTT assay and mitotic index measurement and apoptosis was measured by flow cytometer. The results showed that MnCl2 inhibited A549 cells proliferation in a dose- and time-dependent manner, and induced apoptosis in A549 cells. When G0/G1 cells obtained by serum starvation were incubated with 0.5 mM of MnCl2 in the presence of 10% serum for several time intervals, the disruption of cell cycle progression was observed. The G0/G1 arrest was induced by MnCl2 treatment at 16 h and the arrest maintained for 8 h. Following the G0/G1 arrest, MnCl2 blocked the cells at S phase at 28 h and the S phase arrest maintained for at least 4 h. And moreover, proteasome inhibitor MG132 was able to prolong the duration of G0/G1 arrest induced by MnCl2 treatment. Results of western blotting assay revealed that cellular Cdk4, Cdk2 and phospho-Cdk2 (Thr160) levels decreased in manganese-treated cells at both 20 and 28 h. In addition, the decreasing of Cyclin A level and the increasing of p53 and WAF1/p21 were also induced by MnCl2 treatment at 20 h. The expression of Cyclin D1, Cyclin E and Cdc25A proteins was not altered in manganese-treated cells at both 20 and 28 h. Our results indicate that MnCl2 orderly induces G0/G1 and S phase arrest in A549 cells, the decreasing of Cdk4, Cdk2 and Cyclin A, and the increasing of p53 and Cdks inhibitor WAF1/p21 might be responsible for the G0/G1 arrest, and the decreasing of Cdk4 and Cdk2 levels for the S phase arrest.


Data Collection and Harmonization in HIV Research: The Seek, Test, Treat, and Retain Initiative at the National Institute on Drug Abuse.
Large-scale, multisite data sets offer the potential for exploring the public health benefits of biomedical interventions. Data harmonization is an emerging strategy to increase the comparability of research data collected across independent studies, enabling research questions to be addressed beyond the capacity of any individual study. The National Institute on Drug Abuse recently implemented this novel strategy to prospectively collect and harmonize data across 22 independent research studies developing and empirically testing interventions to effectively deliver an HIV continuum of care to diverse drug-abusing populations. We describe this data collection and harmonization effort, collectively known as the Seek, Test, Treat, and Retain Data Collection and Harmonization Initiative, which can serve as a model applicable to other research endeavors.


Development of a Cell-based Neutralizing Antibody Assay for Zinpentraxin Alfa: Challenges and Mitigation Strategies.
Therapeutic protein drugs can potentially induce immune responses in patients and result in the production of anti-drug antibodies (ADAs), including a subset of ADAs called neutralizing antibodies (NAbs) that might cause loss of efficacy by inhibiting clinical activities of the drug. Herein, we describe the unique challenges encountered during the development of a fit-for-purpose cell-based NAb assay for a new protein modality, zinpentraxin alfa, including our strategies for assay design to overcome various matrix interferences and improve assay drug tolerance. We demonstrated that a typical biotin-drug extraction with acid dissociation (BEAD) approach alone was not sufficient to eliminate matrix interferences in this assay. Instead, the combination of the BEAD and ZebaTM spin size exclusion plate (SEP) was required to achieve the desirable assay performance. We also demonstrated that appropriate acidic buffers were critical in sample pretreatment to improve assay drug tolerance, which not only dissociated the drug/NAb immune complex but also effectively and irreversibly denatured the free drug. The final assay performed well with confirmed assay robustness and suitability for the clinical applications.


ATP-binding cassette transporter A1 expression disrupts raft membrane microdomains through its ATPase-related functions.
ATP-binding cassette transporter A1 (ABCA1) is known to mediate cholesterol efflux to lipid-poor apolipoprotein A-I. In addition, ABCA1 has been shown to influence functions of the plasma membrane, such as endocytosis and phagocytosis. Here, we report that ABCA1 expression results in a significant redistribution of cholesterol and sphingomyelin from rafts to non-rafts. Caveolin, a raft/caveolae marker also redistributes from punctate caveolae-like structures to the general area of the plasma membrane upon ABCA1 expression. Furthermore, we observed significant reduction of Akt activation in ABCA1-expressing cells, consistent with raft disruption. Cholesterol content in the plasma membrane is, however, not altered. Moreover, we provide evidence that a non-functional ABCA1 with mutation in an ATP-binding domain, A937V, fails to redistribute cholesterol, sphingomyelin, or caveolin. A937V also fails to influence Akt activation. Finally, we show that apolipoprotein A-I preferentially associates with non-raft membranes in ABCA1-expressing cells. Our results thus demonstrate that ABCA1 causes a change in overall lipid packing of the plasma membrane, likely through its ATPase-related functions. Such reorganization by ABCA1 effectively expands the non-raft membrane fractions and, consequentially, pre-conditions cells for cholesterol efflux.


[Combination of arterial and venous vascular diseases].
The coincidence of arterial and venous vascular diseases in the region of the extremities is demonstrated. The frequency and the pathophysiological connections are explained and a subdivision of the different forms of combination is made. The therapy has to orient itself at the pathophysiological processes of the individual case, where the arterial as well as the venous vascular region is to be included in the treatment.


Pulmonary histiocytosis X: comparison of radiographic and CT findings.
The authors retrospectively evaluated radiographs, computed tomographic (CT) scans, and results of pulmonary function tests (when available) for 17 patients with biopsy-proved pulmonary histiocytosis X. In 11 patients, high-resolution CT was used. In 12 patients, CT demonstrated cystic air spaces, usually less than 10 mm in diameter. In three of these 12, cysts were the only abnormality, but in six others, nodules (usually less than 5 mm in diameter) were also present. Two patients had only nodules and one, only emphysema. CT showed that many lesions that appeared reticular on plain radiographs were actually cysts. CT showed no central or peripheral concentration of lesions, but it did reveal that many small nodules were distributed in the centers of secondary lobules around small airways. CT findings correlated better with the diffusing capacity (rho = -0.71) than did the plain radiographic findings (rho = -0.57). Thus, CT was better than radiography at showing the morphology and distribution of lung abnormalities.


Results of a large scale onchocercosis survey in Enugu State, Nigeria.
The prevalence of onchocercosis was determined in three Local Government Areas (Ezeagu, Oji-River and Uzo-Uwani) in Enugu State, Eastern Nigeria between March 1989 and June 1990. Enugu State was shown to be mesoendemic for onchocercosis. A total of 7472 (26.9%) persons out of 27,831 examined were positive for skin microfilariae. There was no significant difference in infection rates between males (27.6%) and females (26.2%). Of the 118 villages surveyed only five had no inhabitant with skin microfilariae. There was a progressive increase of prevalence to the second decade of life, although 96.6% of cases with skin microfilariae had only a light infection. Onchocercomata prevalence was recorded as 27.3% which tallies with the prevalence of skin microfilariae at 26.9% hence onchocercomata prevalence may be used as a yardstick for predicting skin microfilariae prevalence.


Association between parent mental health and paediatric TBI: epidemiological observations from the 1987 Finnish Birth Cohort.
This study examined whether parental mental illness has implications for child risk for traumatic brain injuries (TBI). Data on 60 069 Finnish children born in 1987 and their parents were examined for demographic and mental health-related variables in relationship with paediatric TBI. Altogether, 15 variables were derived from the cohort data with ICD-10 F-codes being available for mental health diagnoses for all parents. Bivariate and multivariate analyses were carried out using inpatient and outpatient diagnoses of child TBI. Paternal disorders due to psychoactive substance use (F10-F19) was associated with an increased inpatient TBI (OR=1.51; CI=1.07 to 2.14). Mood disorders (F30-F39) were associated with higher rates of outpatient TBI (OR=1.42; CI=1.06 to 1.90). Paternal personality and behavioural disorders (F60-F69) were linked with a twofold increase in risk across both categories of child TBI (OR=2.35; CI=1.41 to 3.90) and (OR=2.29; CI=1.45 to 3.61), respectively. Among the maternal mental health factors associated with child TBI, schizophrenia and other non-mood psychotic disorders (F20-F29) were associated with an increase in inpatient traumatic brain injuries (iTBI) (OR=1.78; 1.22 to 2.59). Mothers having mood disorders (F30-F39) were more likely to have had a child who experienced an iTBI (OR=1.64; CI=1.20 to 2.22). Mothers with personality and behavioural disorders (F60-F69) were also found to have had children with an increased risk for iTBI (OR=2.30; CI=1.14 to 3.65). Taken together, these data should call attention to methods and strategies designed to augment and support caregiving environments with modalities that can foster mutually supportive households in cooperation with parents who have been diagnosed with a mental disorder.


Amylose selectively includes one from a mixture of two resemblant polyethers in vine-twining polymerization.
In this paper, we describe that amylose almost selectively includes poly(tetrahydrofuran) (PTHF) from a mixture of poly(oxetane) (POXT) and PTHF having resemblant chemical structures and molecular weights in vine-twining polymerization. This was performed by the phosphorylase-catalyzed enzymatic polymerization of alpha-D-glucose 1-phosphate from maltoheptaose as a primer in the presence of a mixture of POXT and PTHF to produce an amylose-PTHF inclusion complex.


Case of complete mesh migration into the stomach after mesh hiatoplasty for a hiatal hernia.
Mesh migration is a rare complication of surgery for a hiatal hernia. Here, we present the case of a 72-year-old who complained of dysphasia and bodyweight loss. Upper gastrointestinal endoscopy revealed incarcerated mesh in the lumen of the esophagogastric junction. Surgery was performed under both endoscopy and laparoscopy, and the mesh was successfully removed via gastrostomy. To the best of our knowledge, our case is the first in which mesh that had migrated into the esophagogastric junction was removed by a combination of laparoscopic and endoscopic procedure, although the cases of 17 patients in which mesh migrated into the stomach after mesh hiatoplasty have previously been reported in the literature.


Modeling growth of one-dimensional islands: influence of reactive defects.
Influence of reactive defects on size distribution of one-dimensional islands is studied by means of kinetic Monte Carlo simulations in combination with an analytical approach. Two different models are examined: a model with anisotropically diffusing atoms irreversibly aggregating to islands, and a reversible model close to thermal equilibrium which allows atom detachment from islands during the growth. The models can be used to simulate island growth of group III metals deposited on the Si(100)2 x 1 surface at room temperature: Al, Ga (irreversible model), and In (equilibrium model). We demonstrate that concentration of the reactive defects 0.0025 per site may change the island size distribution from monomodal to monotonically decreasing in the case of the irreversible model. At concentration >or=0.005 defects per site, a difference between results of the studied models is suppressed by the influence of the defects and similar island size distributions are obtained.


Effect of season on scrotal circumference, semen characteristics, seminal plasma composition and spermatozoa motility during liquid storage in INRA180 rams.
The present study was undertaken to assess the effect of seasons on scrotal circumference, semen characteristics, seminal plasma composition, and sperm motility during liquid storage of INRA180 rams. The semen was collected from five mature INRA180 rams (2-3 years of age) during one year (from April 2014 to March 2015). Scrotal circumferences, semen characteristics, some biochemical parameters of seminal plasma were evaluated. Immediately after collection and evaluation, the semen was pooled and extended in skim milk (SM) at 15°C to reach 0.8×109 spermatozoa/ml. Thereafter, samples were evaluated at different storage times (0, 8, and 24h). The results showed that scrotal circumference, semen quality and the concentration of total protein in seminal plasma were relatively constant during the year (P>0.05). However, total lipid and cholesterol concentrations increased significantly (P<0.001) in winter and summer. The result showed also that progressive motility was higher in winter and summer after 24h of storage (P<0.01). In contrast, no difference was recorded regarding total motility (P>0.05). To conclude, the INRA180 rams have the ability to produce semen with high quality all over the year. The only parameters showing seasonal variations are cholesterol, total lipid, and progressive motility.


SingStrong-A singing and breathing retraining intervention for respiratory and other common symptoms of long COVID: A pilot study.
Management of Long COVID (LC) is hugely challenging for clinicians. This pilot study evaluated a breathing retraining and singing programme (SingStrong for LC) to address common LC symptoms. The study hypothesized that this intervention would improve symptoms impacting disordered breathing and participant wellbeing. The 10-week, bi-weekly online programme was comprised of a 45-min class of mindfulness, breathing retraining, vocal exercises, and singing. Sessions were recorded for non-attenders and conducted by a trained vocal coach experienced in respiratory cohorts. Persons with a confirmed COVID-19 diagnosis and persisting symptoms were invited to participate. Demographic and COVID-19 data were collected, and the DePaul Symptom Questionnaire Short Form (DSQ- SF) and COVID-19 Yorkshire Rehab Screen questionnaires were administered. Post-intervention focus groups were also conducted. Of 27 (F = 23(85%)) participants recruited, data from 21 who completed at least 10 (50%) classes were analysed. Participants showed significant pre-post-intervention improvements in all breathlessness symptoms (at rest: P < 0.001; dressing: P = 0.01; stairs: P < 0.001), fatigue (P = 0.03), usual activities (P = 0.04), pain/disability (P = 0.03), voice quality (P = 0.01), and communication/cognition (P = 0.04). Pre-post number of instances meeting DSQ-SF criteria for myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) decreased by a net of nine cases (14.3%). No association between COVID-19 hospitalisation status and diagnosis of ME/CFS was identified. Qualitative feedback from eight participants was overwhelmingly positive with all reporting improvements in breathing and general well-being. The SingStrong programme shows promise as a viable treatment option for LC sufferers. Future studies are required to further investigate the efficacy of this intervention.


Electrographic seizures and periodic discharges after intracerebral hemorrhage.
To determine the frequency and significance of electrographic seizures and other EEG findings in patients with intracerebral hemorrhage (ICH). We reviewed 102 consecutive patients with ICH who underwent continuous electroencephalographic monitoring (cEEG). Demographic, clinical, radiographic, and cEEG findings were recorded. Using multivariate logistic regression analysis, we determined factors associated with 1) electrographic seizures, 2) periodic epileptiform discharges (PEDs), and 3) poor outcome (death, vegetative or minimally conscious state) at hospital discharge. Seizures occurred in 31% (n = 32) of patients with ICH, prior to cEEG in 19 patients. Eighteen percent (n = 18) of patients had electrographic seizures; only one of these patients also had clinical seizures while on cEEG. After controlling for demographic and clinical predictors, only an increase in ICH volume of 30% or more between admission and 24-hour follow-up CT scan was associated with electrographic seizures (33% vs 15%; OR 9.5, 95% CI 1.7 to 53.8). PEDs were less frequently seen in those with hemorrhages located at least 1 mm from the cortex (8% vs 29%; OR 0.2, 95% CI 0.1 to 0.7). PEDs were independently associated with poor outcome (65% vs 17%; OR 7.6, 95% CI 2.1 to 27.3). In patients with electrographic seizures, the first seizure was detected within the first hour of cEEG monitoring in 56% and within 48 hours in 94%. Seizures occurred in one third of patients with intracerebral hemorrhage (ICH) and over half were purely electrographic. Electrographic seizures were associated with expanding hemorrhages, and periodic discharges with cortical ICH and poor outcome. Further research is needed to determine if treating or preventing seizures or PEDs might lead to improved outcome after ICH.


Highlighting the uniqueness in dielectrophoretic enrichment of circulating tumor cells.
Circulating tumor cells (CTCs) play an essential role in the metastasis of tumors, and thus can serve as a valuable prognostic factor for malignant diseases. As a result, the ability to isolate and characterize CTCs is essential. This review underlines the potential of dielectrophoresis for CTCs enrichment. It begins by summarizing the key performance parameters and challenges of CTCs isolation using microfluidics. The two main categories of CTCs enrichment-affinity-based and label-free methods-are analysed, emphasising the advantages and disadvantages of each as well as their clinical potential. While the main argument in favour of affinity-based methods is the strong specificity of CTCs isolation, the major advantage of the label-free technologies is in preserving the integrity of the cellular membrane, an essential requirement for downstream characterization. Moving forward, we try to answer the main question: "What makes dielectrophoresis a method of choice in CTCs isolation?" The uniqueness of dielectrophoretic CTCs enrichment resides in coupling the specificity of the isolation process with the conservation of the membrane surface. The specificity of the dielectrophoretic method stems from the differences in the dielectric properties between CTCs and other cells in the blood: the capacitances of the malignantly transformed cellular membranes of CTCs differ from those of other cells. Examples of dielectrophoretic devices are described and their performance evaluated. Critical requirements for using dielectrophoresis to isolate CTCs are highlighted. Finally, we consider that DEP has the potential of becoming a cytometric method for large-scale sorting and characterization of cells.


Spatial and temporal variability of ambient air toxics data.
This paper summarizes information on the spatial and temporal variability of selected air toxics pollutants collected on a national basis primarily for a period encompassing 1990-2003. Spatial information on pollutant concentrations is characterized in terms of within-city and between-city variability. Temporal information is summarized as diurnal and seasonal variability and in multiyear trends. The information on variability is presented in the framework of a larger need for systematic documentation of information on air toxics pollutants to assess progress in air pollution control programs.


Esophagocardiomyotomy--floppy Nissen fundoplication effectively treats achalasia without causing esophageal obstruction.
Effective surgical treatments for achalasia of the esophagus facilitate swallowing by division of muscles that fail to relax normally during swallowing. If esophagocardiomyotomy is performed, a complementary antireflux procedure is mandatory to prevent postoperative gastroesophageal reflux. We evaluated patients who had undergone a circumferential antireflux procedure after esophagocardiomyotomy to determine the effects of this procedure in patients with an aperistaltic esophagus. During the past 15 years we treated 94 patients with achalasia by use of pneumatic dilation (66), esophageal myotomy (19), or esophagocardiomyotomy with floppy Nissen fundoplication (24). Achalasia was defined by radiographic and manometric criteria until 1986 when computerized axial manometry of the esophagus was initiated, providing information about the three-dimensional contour and "volume" of the lower esophageal sphincter in addition to the usual manometric data. Dysphagia was effectively relieved in all, and neither postoperative reflux nor esophageal obstruction was observed after esophagocardiomyotomy followed by floppy Nissen fundoplication. The measured lower esophageal sphincter pressures and sphincter volume were markedly reduced. Esophagocardiomyotomy with floppy Nissen fundoplication is an effective treatment for achalasia; clinical evidence of obstruction of the esophagus was not seen, and manometric data were typical of a weakened sphincter.


Interference Effects of Different Resistance-Training Protocols on Rowing Ergometer Performance: A Study on Semiprofessional Rowers.
To evaluate the interference effects of various resistance-training (RT) protocols on rowing ergometer performance. Fourteen semiprofessional male rowers randomly completed 5 protocols in separate sessions: (1) control-no RT session was performed, (2) upper-body high-fatigue-4 sets to failure during the bench pull exercise, (3) upper-body low-fatigue-4 sets of 6 repetitions during the bench pull exercise, (4) lower-body high-fatigue-4 sets to failure during the leg-press exercise, and (5) lower-body low-fatigue-4 sets of 6 repetitions during the leg-press exercise. All sets were performed against the 12-repetition-maximum load with 2 minutes of interset rest. Following the completion of the protocols, subjects performed an all-out 1000-m rowing ergometer test. Compared with the control condition, rowing ergometer performance was not significantly affected after the low-fatigue RT protocols (upper body: P ≥ .487; Δ = 0.0%-0.2%; lower body: P ≥ .200; Δ = -0.2%-0.5%), while it significantly declined following high-fatigue RT protocols (upper body: P ≤ .001; Δ = 1.0%-2.0%; lower body: P ≤ .002; Δ = 2.1%-2.5%). The average heart rate was significantly lower for the control condition compared with all RT protocols (P ≤ .043; Δ = 1.0%-1.5%). To minimize interference on rowing performance, coaches should prioritize the level of effort in RT protocols over specific exercises, specifically avoiding high-fatigue protocols that lead to failure before rowing practice.


Molecular water on exposed Al3+ cations is a source of acidity in silicoaluminas.
Evidence about the remarkable acidic nature of molecular water adsorbed at the surface of mesoporous MCM-41 silicoaluminas (MSA) with a ratio of Si/Al = 25 is reported, coming from both infrared spectroscopy and ab initio calculations. By using CO as a probe, OH stretching and HOH bending modes of water adsorbed on coordinatively unsaturated Al ions (Lewis sites) at the surface of MSA have been detected for the first time. CO adsorption causes OH stretching frequencies to suffer a bathochromic shift of about -200/-250 cm(-1), whereas the HOH bending frequency undergoes a hypsochromic shift by about +10/+20 cm(-1). B3LYP/6-31+G(d,p) calculations on model clusters designed to mimic both Brønsted and Lewis sites validate the assignments, showing that water adsorbed on the surface Lewis site, when interacting with CO, shows an acidity comparable to that of a classical zeolitic Brønsted site.


Histochemical characteristics of parafollicular cells and medullary thyroid carcinoma.
Normal canine parafollicular cells share a common set of histochemical characteristics, which include masked metachromasia and argyrophilia, with human as well as rat medullary thyroid carcinomas. Masked metachromasia, a property of polypeptide hormone-producing cells, was demonstrated by staining with toluidine blue or coriophosphine O after acid hydrolysis. Argyrophilia was demonstrated both by the Grimelius silver nitrate technic and by the Azzopardi modification of the Bodian method. With these technics, parafollicular cells in the dog and medullary carcinoma of human and rat origin showed nearly identical staining reactions. Fixation in glutaraldehyde was superior to formaldehyde in demonstrating masked metachromasia of normal dog parafollicular cells, while formaldehyde fixation was superior for the demonstration of argyrophilia of granules. In general, the Grimelius method was superior to the Azzopardi modification of the Bodian technic for the demonstration of argyophilia. The results of this study provided further support for the parafollicular cell origin of human and rat medullary thyroid carcinomas and also provided a useful set of histochemical criteria for the diagnosis of this neoplasm.


[Impact of ultrasonographic vascular mapping on constructing autogenous arteriovenous fistulas for permanent hemodialysis access?].
We used high resolution ultrasonography to identify usable veins and arteries in the forearm for creation of autogenous arteriovenous fistulas (AVF) for permanent hemodialysis access. The effect of preoperative vascular mapping followed by intraoperative controls on the outcome of AVF should be reported. study subjects were adults referred for primary permanent hemodialysis access between January 2001 and November 2002. In all patients sonographic assessment was performed before surgical evaluation. A feeding artery was considered adequate if the diameter was more than 1.5 mm, the vein more than 2.0 mm. All AVF were controlled by intraoperative sonographic measurements of PSV and diameter of the fistula-vein. AVF were placed in 94.1% of all patients. The early failure rate of AVF was 6.3%. Primary patency rate of AVF after 24 hours: 93.7%, after 30 days: 91.4%, after 3 months: 86.9%, preliminary patency rate after 1 year: 70.1%. No unsuccessful surgical explorations were performed. 85.5 % of AVF were constructed as forearm fistulas. Suboptimal vessels (artery < 2.0 mm, vein < 3.0 mm) were used in 31.3% of patients. Patency rates did not differ in this subgroup. In 2 patients synthetic grafts were placed because of non-maturation of AVF. In 15 patients the AVF had to be cannulated by experts for 3 to 6 months. 50.0% of all AVF were constructed in diabetic patients. Patency rates were equal to that of non-diabetic patients. No patient suffered on signs of steal-syndrome. the assessment of forearm vessels by high resolution sonographic vascular mapping helps to find the optimal location for constructing an arteriovenous wrist fistula in almost all patients needing a permanent hemodialysis access. The aggressive approach to the creation of autogenous fistulas could be realized without unsuccessful surgical explorations and with a minimal early failure rate, a high maturation rate including patients with diabetes mellitus and no signs of steal-syndrome


[Effects of kuo guan powder on immunologic functions in patients with ben-xu biao-shi syndrome in ischemic heart disease].
Ischemic heart disease (IHD) is correlated with the Immunodisturbances. In this study, the immunological effects of Kuo Guan No 1, a powder for aiding Qi and activating the blood, in 17 cases of Qi Yang Xu Xue Yu (QYXXY, ) syndrome, Kuo Guan No 2, powder for nourishing the Yin and activating the blood, in 14 cases of Yin-Xu Xue-Yu (YXXY, ) syndrome had been observed in one month treatment. After treatment with both powder of Kuo Guan No 1 and Kuo Guan No 2, the increased levels of IgG, CIC, IC-IgG and IC-C3 in serum and the numbers of B cells in peripheral blood lymphocyte (PBL) of the patients with Ben-Xu Biao-Shi (BXBS, ) syndrome of IHD angina were markedly decreased and showed no significant difference while compared with the normal controls (P greater than 0.05); the numbers of OKT+3, OKT+4 and OKT+8 cells in PBL, which were lower before treatment in both groups, were obviously increased and showed no marked difference with the controls (P greater than 0.05); the higher ratio of T4/T8 was lowered in group of YXXY syndrome, and showed no difference while compared with the controls (P greater than 0.05), but the ratio in QYXXY syndrome group was lowered than that in the controls (P less than 0.05). After the treatment with Kuo Guan No 1, the increased level of C3 in serum in QYXXY group was lowered down to that of the controls (P greater than 0.05). The results indicated that it is reasonable to consider that "Kuo Guan" powder is an immunoregulative preparation for patients with BXBS syndrome of IHD angina.


Comparison of the CAGE questionnaire versus some biochemical markers in the diagnosis of alcoholism.
We have compared the individual sensitivity, specificity and predictive value of the CAGE questionnaire, plasma levels of ethanol and acetate, mean corpuscular volume (MCV), gamma glutamyl transferase (GGT), and glycosylated haemoglobin (Hb A1c) in a group of 50 healthy non-alcoholic controls and 31 patients with non-alcoholic liver disease (Group I), and in a second group of 40 alcoholic patients (Group II). Taken individually, the CAGE questionnaire was the most efficient (96% sensitive and 92% specific), followed by plasma levels of acetate (74% sensitive and 85% specific), MCV (64% sensitive and 91% specific) and GGT (72% sensitive and 80% specific). Hb A1c did not show any statistically significant difference between alcoholics and non-alcoholics and thus is of no use as a screening test for the diagnosis of alcoholism. Furthermore, we attempted to design a discrimination procedure to separate alcoholics from controls and patients with non-alcoholic hepatic diseases using a combination of the most promising tests. The most powerful discrimination model was constructed with the four questions of the CAGE questionnaire. The percentage of correct classifications using this model was 99% from Group I (specificity) and 90% from Group II (sensitivity). The CAGE questionnaire was itself so useful as a discriminant in our sample that no increased diagnostic efficacy was noticed on adding any of the other tests. Using objective variables (MCV, acetate and GGT) as discriminants, we could correctly classify 96% of subjects from Group I (specificity) and only 64% from Group II (sensitivity).


Suppression of skin lesions by transdermal application of CpG-oligodeoxynucleotides in NC/Nga mice, a model of human atopic dermatitis.
Atopic dermatitis (AD) is a pruritic inflammatory skin disease characterized by an elevation of the total IgE level in plasma, the infiltration of mast cells and eosinophils, and the expression of cytokines by Th2 cells. NC/Nga mice kept in conventional conditions are known to develop skin lesions resembling human AD. We examined in this study the alterations of immune response in NC/Nga mice kept in conventional conditions, following transdermal application of CpG-oligodeoxynucleotides (ODN), which plays a critical role in immunity via the augmentation of Th1-type and suppression of Th2-type responses. CpG-ODN remarkably changed the immune response from type Th2 to Th1 as determined from cytokine mRNA and Ab levels. The serum IgE level was decreased and the expression of IgG2a was up-regulated. The application of CpG-ODN to the skin also decreased inflammatory infiltration of mast cells, and suppression in the skin lesions was observed. Furthermore, the generation of regulatory T cells, which are considered immune suppressive T cells, was observed in the skin on treatment with CpG-ODN. These results suggested CpG-ODN is effective for immunotherapy in patients with AD, which is characterized by Th2-dominated inflammation.


Nutraceuticals in the Modulation of the Intestinal Microbiota: Current Status and Future Directions.
Pharmaceutical interest in the human intestinal microbiota has increased considerably, because of the increasing number of studies linking the human intestinal microbial ecology to an increasing number of non-communicable diseases. Many efforts at modulating the gut microbiota have been made using probiotics, prebiotics and recently postbiotics. However, there are other, still little-explored opportunities from a pharmaceutical point of view, which appear promising to obtain modifications of the microbiota structure and functions. This review summarizes all in vitro, in vivo and clinical studies demonstrating the possibility to positively modulate the intestinal microbiota by using probiotics, prebiotics, postbiotics, essential oils, fungus and officinal plants. For the future, clinical studies investigating the ability to impact the intestinal microbiota especially by using fungus, officinal and aromatic plants or their extracts are required. This knowledge could lead to effective microbiome modulations that might support the pharmacological therapy of most non-communicable diseases in a near future.


The motor agitation and retardation scale: a scale for the assessment of motor abnormalities in depressed patients.
Increasing recognition of the neurologic aspects of depressive disorder has aroused new interest in the potential neuropathologic significance of "psychomotor" symptoms in depression. Psychomotor symptoms have yet to be clearly defined, however. The Motor Agitation and Retardation Scale (MARS) was developed to provide a comprehensive and nonredundant measure of the motor abnormalities associated with agitation and retardation in depression. Forty-one depressed in patients and 20 normal control subjects were assessed. In this sample, the MARS provided a reliable and valid scale for the clinical assessment of 19 abnormal motor behaviors associated with agitation and retardation in depression. The MARS may be useful for investigation of the pathophysiologic significance of various manifestations of motor abnormalities in depression and, as part of a larger battery, for the investigation of the relative contribution of motor abnormalities to psychomotor impairment in depression.


Isolation of the salmonid rhamnose-binding lectin STL2 from spores of the microsporidian fish parasite Loma salmonae.
The microsporidian parasite, Loma salmonae, is the causative agent of gill disease in both wild and netpen-reared salmonids worldwide. In this paper we report the finding of a rhamnose-binding lectin from steelhead trout, Oncorhynchus mykiss, which was found bound in high concentration to the surface coat of L. salmonae spores. SDS-PAGE, immunoblot, N-terminal sequencing and mass spectrometric analyses were used to determine that the dominant 24 kDa protein lectin observed on SDS-PAGE analysis of intact spore extracts is the O. tshawytscha variant of the previously identified rhamnose-binding lectin STL2 from rainbow trout, O. mykiss. Although the physiological role of these lectins has not been clearly delineated, they have been implicated in a variety of functions, including inhibition of pathogenic bacteria by opsonization and macrophage-mediated tumour lysis.


Biochemical purification and characterization of a truncated acidic, thermostable chitinase from marine fungus for N-acetylglucosamine production.
N-acetylglucosamine (GlcNAc) is widely used in nutritional supplement and is generally produced from chitin using chitinases. While most GlcNAc is produced from colloidal chitin, it is essential that chitinases be acidic enzymes. Herein, we characterized an acidic, highly salinity tolerance and thermostable chitinase AfChiJ, identified from the marine fungus Aspergillus fumigatus df673. Using AlphaFold2 structural prediction, a truncated Δ30AfChiJ was heterologously expressed in E. coli and successfully purified. It was also found that it is active in colloidal chitin, with an optimal temperature of 45°C, an optimal pH of 4.0, and an optimal salt concentration of 3% NaCl. Below 45°C, it was sound over a wide pH range of 2.0-6.0 and maintained high activity (≥97.96%) in 1-7% NaCl. A notable increase in chitinase activity was observed of Δ30AfChiJ by the addition of Mg2+, Ba2+, urea, and chloroform. AfChiJ first decomposed colloidal chitin to generate mainly N-acetyl chitobioase, which was successively converted to its monomer GlcNAc. This indicated that AfChiJ is a bifunctional enzyme, composed of chitobiosidase and β-N-acetylglucosaminidase. Our result suggested that AfChiJ likely has the potential to convert chitin-containing biomass into high-value added GlcNAc.